We propose to study the mechanism by which cholesterol esters are formed in the reaction catalyzed by lecithin:cholesterol acyltransferase(LCAT). The studies of LCAT will focus on two problems. First, we will study the activation of the enzyme by a homologous series of synthetic peptides which we propose to synthesize. This series is based on a parent synthetic peptide of 20 residues which has 65% of the LCAT activating capacity of the native activator, apoA-I from human plasma high density lipoproteins(HDL). This series of peptides will allow us to determine the importance of charge, hydrophobicity, and lipophilicity to enzyme activity. The second problem is to demonstrate that a reassembled lipid-protein complex will form an HDL similar to that found in man. The structural changes in the complexes will be monitored by physical methods. These studies will provide a better understanding of cholesterol metabolism in man and should be useful in any rational approach to an overall understanding of lipid metabolism and its relationship to atherosclerosis.